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Cell and Membrane Dynamics of Parasite-Host Interactions

Grenoble, the Metropole of the Alps : Land of excellences and innovation

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Located in the south-east France, nestled in the heart of three mountains, the Chartreuse, Belledonne and Vercors with, at its doors, several national and regional parks in the Alps, Grenoble is a ideal city to combine higher education and diploma with love of nature. Capital of ski and Olympic city, close to twenty ski resorts, its surroundings and the campus allow the practice of all sports, including for high-level sports students. About 65,000 students across the city contribute to a young, athletic and multicultural population.

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Ranked in the Top 5 most innovative cities in the world in particular in sectors such as micro- and nanotechnologies, software, life sciences, energy ..., Grenoble has a strategic position to promote privileged networking between laboratories, universities (University of Grenoble Alpes,UGA), local and international prestigious engineering schools and companies to work together for the world of tomorrow.

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At the heart of the Grenoble University campus Santé, the Institute for Advanced Biosciences/IAB is excellently positioned to lead the way in innovative Health and Medicine by actively promoting basic and translational biomedical research committed to cutting edge discovery and translational research on Epigenetics, Chronic Diseases and Cancer. To this end the IAB develops long-term bonds with the neighbouring top level Research Institutes. These include the « Interdisciplinary Laboratory of Physics, LIPhy, Institute of Neurosciences, GIN ; Institute of Structural Biology, IBS ; Institute for electronics and information technologies, CEA-Leti, Institute of Biosciences and Biotechnologies of Grenoble, CEA-BIG… » and offer unique opportunities for multi-disciplinary research programs and networks to foster one of the most highly-competitive research center for the reinvention of Health and Medicine.

News

23/7/19 Check our new publication

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15/6/19 Integration of the team into the ParaFrap Labex-Consortium

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18/2/19 New publication in Médecine Sciences

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Bastien's and Valeria's son Gabriele came in our world! Congratulations!

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17/12/18 Isabelle Tardieux co-organizer of the Conference on Mechanotransduction of Host-Pathogen Interactions

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9/12/18 Georgios presented his research at the ASCB meeting in San Diego, California.

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20/10/18 New publication

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22/7/18 Master 1 and 2 positions available in live imaging and nanophysics. Contact Isabelle Tardieux for more info​​

Toxoplasma gondii

"In 1908, while working at the Pasteur Institute in Tunis, Charles Nicolle and Louis Manceaux discovered a protozoan organism in the tissues of a hamster-like rodent known as the gundi, Ctenodactylus gundi. Although Nicolle and Manceaux initially believed the organism to be a member of the genusLeishmania that they described as "Leishmania gondii", they soon realized they had discovered a new organism entirely; they re-named it Toxoplasma gondii. The new genus name Toxoplasma is a reference to its morphology: Toxo, from Greek τόξον (toxon, "arc, bow"), and πλάσμα (plasma, "shape, form") and the host in which it was discovered, the gundi (gondii). The same year Nicolle and Mancaeux discovered T. gondii, Alfonso Splendore identified it in a rabbit in Brazil.

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The first conclusive identification of T. gondii in humans was in an infant girl delivered full term by Caesarean section on May 23, 1938, at Babies' Hospital in New York City. When she died at one month of age, an autopsy was performed. Lesions discovered in her brain and eye tissue were found to have both free and intracellular T. gondii'."

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Dubey JP (July 2009). "History of the discovery of the life cycle of Toxoplasma gondii". International Journal for Parasitology. 39 (8): 877–82. doi:10.1016/j.ijpara.2009.01.005 (Wikipedia)

Apicomplexa form a large phylum of unicellular eukaryotic microbes,

some of which are responsible for devastating diseases in humans.

The deadliest member, Plasmodium spp., which causes malaria, kills around 400 000 people annually. The most widespread, Toxoplasma/T. gondii, is silently hosted in about a third of the human population worldwide. However, this population remains at serious risk for severe toxoplasmosis with life-threatening cerebral or cardiac pathologies in case they experience immunosuppression. Indeed, while the immune system usually controls the early and transient expansion of the T. gondii population after oral ingestion, it also concomitantly favors dissemination through the vascular compartments and further promotes long-term persistence of a slow replicative parasite subpopulation in particular in the central nervous system. Even of short duration, any immunosuppression can switch on the replicative developmental program, which if left uncontrolled is lethal. Furthermore severe cases of systemic acute toxoplasmosis in immune-competent humans are more and more observed in South America and Asia, and have been correlated with atypical non-human adapted genotypes of T. gondii. Finally, fetuses also represent a population at risk of T. gondii-induced prenatal development problems possibly leading to death in utero, in primo-parasitized pregnant women due to placenta and fetus colonization.

Research

Accounting for initiation of tissue acute damages is the striking ability of tachyzoite to invade about any metazoan nucleated cells. Once enclosed in a peculiar compartment, the tachyzoite multiplies until the former fills most of the host cell cytoplasm: the progeny actively exits prior invading other cells, thus amplifying locally or more distantly the parasitic process in the hosts.

Tachyzoites are several micron-sized ellipsoid polarized cells that glide on substrates at speeds of several microns per second, an order of magnitude faster that the fastest human cells. They also penetrate into their target cells within a few tens of seconds in sharp contrast with the minute-scale of macropinocytosis/phagocytosis used by many other intracellular microbes.

- Achieve a comprehensive dynamic model of how the tachyzoite generates force(s) to move towards and invades target cells under 2D and 3D microenvironments.

RESEARCH THEME 2

- Provide nanoscale structural and functional characterization of the “RON invasive nanodevice” prior and upon injection into the target cell membrane/cortex, a device key to initiate and support active invasion.

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In the same line, we are interested in understanding how a tachyzoite subpopulation reaches and colonizes the so-called priviledged tissues in which T. gondii switches to the slow replicative developmental and persistent stage.

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RESEARCH THEME 3

- Decipher how much tachyzoites depend on their own motile skills or/and on host leucocytic « shuttles » to (i) avoid immune killing during the acute phase of parasitism following ingestion of contaminated stages and (ii) sustain parasite dissemination through the host tissues/vasculatures.

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Our basic and trans-disciplinary research programs lie at the interface between parasitology, cell biology and biophysics and require the development of nano-tools and technologies provided through the tight collaboration with physicists (in priority from the LIPhy, Grenoble). The Toxoplasma parasite is not only seen as a widely spread infectious and « potential killer » microbe but also as a fascinating probe unveiling fundamental regulatory mechanisms of cell and tissue homeostasis under constant challenge during asymptomatic and symptomatic phases of parasitism*.

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*In the context of the interdisciplinary spirit of our research, continuous feedback with the neighbor team of Mohamed-Ali Hakimi "Host-pathogen interactions & Immunity to infections" and with the I. Tardieux mentor, Geneviève Milon (Institute Pasteur Paris, Dr Emerit) ground progress in our day after day research.

Invasion by T. gondii proceeds with the tachyzoite injecting a hetero-tetrameric complex, stored in the apical rhoptry organelles, into the recipient Plasma Membrane (PM). This RON complex organizes as an elastic torus that promotes bridging of the two cells through the assembly of a Zoite-Cell Junction (ZCJ). The tachyzoite applies invasive force on the ZCJ to pass through while inducing the budding of an Entry Vesicle (EV). The EV derives from PMcomponents sieved at the ZCJ and once released in the host cell cytoplasm, evolves as a Parasitophorous Vacuole (PV) to support intracellular parasite growth.

Members

Bastien Touquet

Research technician CNRS

Georgios Pavlou

PhD student

Luis Vigetti

Master 1 student

Lea Swales

Bachelor (Licence) student

Former Students

Mateusz Biesaga - Master 1 2016-2017

Irati Pablos - Master 2 2017-2018

Marie-Belle Abboud - Master 2 2016-2017

Juliette Trido - M1 2016-2017

Martin Porret - M1 2017-2018

Jaco Delport - M2 2017-2018

Nadine Ajami - M1 2017-2018

Marion Bichet - M1 2016-2017

Dr Isabelle Tardieux

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Team leader

Research Director CNRS

Dr Patricia Renesto

Research Director CNRS

To join

Dr Geneviève Milon

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Institute Pasteur Emerit

Microscopy

Copyright Isabelle Tardieux lab

Nikon Eclipse Ti microsope using a spinning disk yokogawa. Software and hardware additions to the microscope have been added by Gataka systems (http://www.gataca-systems.com)